Synthesis, and biological evaluation of EGFR/HER2-NAMPT conjugates for tumor treatment
文献类型：期刊论文
| 作者 | Ding, Mengyuan1; Shen, Qianqian2; Lu, Wei1; Zhu, Shulei1 |
| 刊名 | MOLECULAR DIVERSITY
 |
| 出版日期 | 2023-07-23 |
| 页码 | 20 |
| ISSN号 | 1381-1991 |
| 关键词 | EGFR HER2 NAMPT Resistance Selectivity Molecular docking |
| DOI | 10.1007/s11030-023-10701-y |
| 通讯作者 | Lu, Wei(wlu@chem.ecnu.edu.cn) ; Zhu, Shulei(slzhu@chem.ecnu.edu.cn) |
| 英文摘要 | Throughout the reported applications of EGFR inhibitors, it is usually employed with HDAC or other targets to design multi-target inhibitors for cancer treatment. In this paper, we designed a drug conjugate that targeted EGFR & HER2 and had inhibitory activity of NAMPT simultaneously. Compound 20c significantly inhibited the EGFR & HER2 and NAMPT enzyme activities, and had comparable or even higher anti-proliferative activity than lapatinib in various cancer cells with over-expressed EGFR and HER2. Importantly, 20c was expected to increase sensitivity to EGFR inhibitor-resistant cells. In Osimertinib-resistant cells (NCI-1975 cells with the L858R/T790M/C797S triple mutation and Ba/F3 cells with the Del19/T790M/C797S triple mutation), the anti-proliferative activity of compound 20c was increased by more than twofold compared with Osimertinib, so as to obtain better curative effect. This strategy is a promising method of embedding multiple pharmacophores into a single molecule, which lays a good foundation for the design and synthesis of small molecule drug conjugates with strong targeting ability and high cytotoxicity. |
| WOS关键词 | GROWTH-FACTOR RECEPTOR ; EGFR ; CANCER ; RESISTANCE ; INHIBITION ; MOLECULE ; IDENTIFICATION ; EFFICACY ; THERAPY ; TARGET |
| WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| 出版者 | SPRINGER |
| WOS记录号 | WOS:001033666400002 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306773]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Lu, Wei; Zhu, Shulei |
| 作者单位 | 1.East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug Dev, Sch Chem & Mol Engn, Shanghai 200062, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ding, Mengyuan,Shen, Qianqian,Lu, Wei,et al. Synthesis, and biological evaluation of EGFR/HER2-NAMPT conjugates for tumor treatment[J]. MOLECULAR DIVERSITY,2023:20. |
| APA | Ding, Mengyuan,Shen, Qianqian,Lu, Wei,&Zhu, Shulei.(2023).Synthesis, and biological evaluation of EGFR/HER2-NAMPT conjugates for tumor treatment.MOLECULAR DIVERSITY,20. |
| MLA | Ding, Mengyuan,et al."Synthesis, and biological evaluation of EGFR/HER2-NAMPT conjugates for tumor treatment".MOLECULAR DIVERSITY (2023):20. |
入库方式： OAI收割
来源：上海药物研究所
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